Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01363011
First received: May 11, 2011
Last updated: January 10, 2014
Last verified: January 2014

May 11, 2011
January 10, 2014
May 2011
January 2013   (final data collection date for primary outcome measure)
Change from baseline in estimated glomerular filtration rate [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
primary endpoint is the change from baseline to Week 24 in estimated creatinine clearance [ Time Frame: 24 Weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01363011 on ClinicalTrials.gov Archive Site
  • Proportion of participants achieving virologic response (HIV-1 RNA < 50 copies/mL) [ Time Frame: Weeks 24, 48 and 96 ] [ Designated as safety issue: No ]
  • Long term effect of COBI-containing regimens on renal parameters [ Time Frame: Weeks 24, 48, and 96 ] [ Designated as safety issue: Yes ]
    Safety data regarding renal parameters will be summarized.
  • Incidence of adverse events and graded laboratory abnormalities [ Time Frame: Baseline to Week 96 plus 30 days ] [ Designated as safety issue: No ]
    All safety data will be summarized by treatment group.
  • Plasma pharmacokinetics (PK) parameters of COBI as measured by Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½. [ Time Frame: Baseline, Weeks, 2, 4, and 24 ] [ Designated as safety issue: No ]
    • Cmax is defined as the maximum observed concentration of drug in plasma
    • Tmax is defined as the time of Cmax
    • Clast is defined as the last observable concentration of drug
    • Tlast is defined as the time of Clast
    • Ctau is defined as the observed drug concentration at the end of the dosing interval
    • λz is defined as the terminal elimination rate constant
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
    • t1/2 is defined as the estimate of the terminal elimination half-life of the drug
The proportion of subjects achieving virologic response at Weeks 24 and 48 (HIV-1 RNA < 50 copies/mL) [ Time Frame: 24 & 48 Weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
A Phase 3 Open-label Safety Study of Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment

This study is to characterize the effect of Cobicistat based regimens on parameters of renal function in HIV infected patients with mild to moderate renal impairment, and also, to assess the safety and tolerability of those regimens in order to generate appropriate dosing recommendations.

Not Provided
Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acquired Immunodeficiency Syndrome
  • HIV Infections
  • Drug: EVG/COBI/FTC/TDF
    Cohort 1: Single tablet regimen of elvitegravir (EVG) 150 mg/cobicistat (COBI) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg
    Other Name: Stribild®
  • Drug: COBI
    Cobicistat (COBI, /co) 150 mg tablet administered with food orally once daily
    Other Name: Tybost™
  • Drug: ATV
    Atazanavir (ATV) 300 mg tablet administered orally once daily
    Other Name: Reyataz®
  • Drug: DRV
    Darunavir (DRV) 800 mg tablet administered orally once daily
    Other Name: Prezista®
  • Drug: NRTI
    Participants will receive 2 invesigator-selected nucleoside reverse transcriptase inhibitors (NRTIs), which may include abacavir (ABC), combivir, didanosine (DDI), emtricitabine (FTC), epzicom, lamivudine (3TC), tenofovir disoproxil fumarate (TDF), or truvada (TVD), administered according to prescribing information.
  • Experimental: EVG/COBI/FTC/TDF
    Participants will receive EVG/COBI/FTC/TDF STR for 96 weeks.
    Intervention: Drug: EVG/COBI/FTC/TDF
  • Experimental: ATV/co or DRV/co
    Participants will receive ATV/co or DRV/co, plus 2 NRTIs, for 96 weeks.
    Interventions:
    • Drug: COBI
    • Drug: ATV
    • Drug: DRV
    • Drug: NRTI
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
100
June 2014
January 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

Cohort 1 (Treatment Naïve)

  • Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening
  • Screening genotype report must show sensitivity to FTC and TDF
  • No prior use of any approved or investigational antiretroviral drug for any length of time

Cohort 2 (Pharmacoenhancer Switch)

  • Subjects must be receiving atazanavir (ATV) 300 mg/ritonavir (RTV) 100 mg plus 2 NRTIs OR darunavir (DRV) 800 mg/RTV 100 mg plus 2 NRTIs for at least 6 months prior to screening
  • Plasma HIV-1 RNA concentrations at undetectable levels in the 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at screening
  • Subjects experiencing intolerance to RTV (as determined by the Investigator)

Cohort 1 and Cohort 2

  • The ability to understand and sign a written informed consent form
  • Normal ECG
  • Mild to Moderate renal function
  • Stable renal function
  • Hepatic transaminases (AST and ALT) ≤ 5 x the upper limit of the normal range (ULN)
  • Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (subjects with documented Gilbert's Syndrome or hyperbilirubinemia due to atazanavir therapy may have total bilirubin up to 5 x upper limit of normal)
  • Adequate hematologic function
  • Serum amylase ≤ 5 x ULN
  • Males and females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drug
  • Age ≥ 18 years

Exclusion Criteria:

  • New AIDS defining condition diagnosed within the 30 days prior to screening
  • Receiving drug treatment for Hepatitis C, or anticipated to receive treatment for Hepatitis C
  • Subjects experiencing decompensated cirrhosis
  • Females who are breastfeeding
  • Positive serum pregnancy test (female of childbearing potential)
  • Implanted defibrillator or pacemaker
  • Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
  • History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
  • Active, serious infections (other than HIV 1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline
  • Receiving ongoing therapy with any of medications contraindicated for use with EVG, COBI, FTC, TDF, ATV, DRV; or subjects with any known allergies to the excipients of EVG/COBI/FTC/TDF STR, COBI tablets, atazanavir capsules or darunavir tablets or contraindicated for the 2 NRTIs as part of the Cohort 2 regimen
  • Participation in any other clinical trial without prior approval
  • Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Austria,   Canada,   Dominican Republic,   Germany,   Mexico,   Puerto Rico,   United Kingdom
 
NCT01363011
GS-US-236-0118
No
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Javier Szwarcberg, MD Gilead Sciences
Gilead Sciences
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP